Rae C, Karmiloff-Smith A, Lee M A, Dixon R M, Grant J, Blamire A M, Thompson C H, Styles P, Radda G K
MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK.
Neurology. 1998 Jul;51(1):33-40. doi: 10.1212/wnl.51.1.33.
To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits.
WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits.
We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS.
WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time.
The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.
确定威廉姆斯综合征（WS）患者大脑中可能发生哪些生化变化，以及这些变化是否可能与认知缺陷相关。
WS是一种罕见的先天性疾病，具有特征性的身体、语言和行为表型以及已知的认知缺陷。
我们从14名WS患者（年龄8至37岁）和48名年龄相仿的对照者的主要由额叶和顶叶组成的区域获取了31P磁共振波谱（MRS）。将WS队列中获得的定位到左侧小脑的1H MRS（27立方厘米）与16名年龄和性别匹配的正常对照者的进行比较。对所有接受1H MRS检查的受试者进行了一系列认知测试。
WS患者的大脑表现出显著的生化异常。WS患者中所有包含磷酸单酯（PME）峰的31P MRS比率均有显著改变，表明PME显著降低。与对照组相比，WS患者小脑内含胆碱化合物和含肌酸化合物与N-乙酰天门冬氨酸的比率（Cho/NA和Cre/NA）显著升高，而Cho/Cre比率未改变。这表明小脑中神经元标志物N-乙酰天门冬氨酸减少。在小脑比率Cho/NA和Cre/NA与所有受试者在各种神经心理学测试中的能力之间发现了显著相关性，这些测试包括言语和操作智商、英国图片词汇量表、瑞文渐进矩阵测验和检查时间。
这些相关性可以从两种方式来解释：1）我们对小脑神经化学的采样反映了对“整体”大脑神经化学的一种测量，与小脑功能无关；或者2）这些关系表明，在各种认知测试中，小脑神经元完整性是（在发育时间尺度上或实时）能力的一个必要条件。
